Molecular Dynamics Simulations Predict that rSNP Located in the HNF-1α Gene Promotor Region Linked with MODY3 and Hepatocellular Carcinoma Promotes Stronger Binding of the HNF-4α Transcription Factor

Španinger, Eva; Potočnik, Uroš; Bren, Urban

doi:10.3390/biom10121700

Cited by 5 publications

(3 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One study suggests that up to 29% of HNF4A-MODY cases may be incorrectly credited to HNF1A-MODY and sequencing of HNF4A is proposed when there is no mutation in HNF1A [ 127 ]. Recently, it was shown that single nucleotide polymorphism located in the HNF1A gene promoter can affect the binding of HNF4A and subsequently regulate HNF1A gene expression [ 128 ].…”

Section: Diagnosis and Current Treatment Optionsmentioning

confidence: 99%

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

Skoczek

Dulak

Kachamakova‐Trojanowska

2021

IJMS

View full text Add to dashboard Cite

Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous group of monogenic endocrine disorders that is characterised by autosomal dominant inheritance and pancreatic β-cell dysfunction. These patients are commonly misdiagnosed with type 1 or type 2 diabetes, as the clinical symptoms largely overlap. Even though several biomarkers have been tested none of which could be used as single clinical discriminator. The correct diagnosis for individuals with MODY is of utmost importance, as the applied treatment depends on the gene mutation or is subtype-specific. Moreover, in patients with HNF1A-MODY, additional clinical monitoring can be included due to the high incidence of vascular complications observed in these patients. Finally, stratification of MODY patients will enable better and newer treatment options for MODY patients, once the disease pathology for each patient group is better understood. In the current review the clinical characteristics and the known disease-related abnormalities of the most common MODY subtypes are discussed, together with the up-to-date applied diagnostic criteria and treatment options. Additionally, the usage of pluripotent stem cells together with CRISPR/Cas9 gene editing for disease modelling with the possibility to reveal new pathophysiological mechanisms in MODY is discussed.

show abstract

Section: Diagnosis and Current Treatment Optionsmentioning

confidence: 99%

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

Skoczek

Dulak

Kachamakova‐Trojanowska

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Monogenic diabetes, a rare form of diabetes seen in young people (types 4 and 5), is associated with heterozygous mutations in some genes, such as PDX1 and HNF1A. Variants of PDX1 and HNF1A genes are also linked with an increased risk of obesity, T2DM, or hyperglycemia [60][61][62]. Figure 2 summarizes the different mechanisms that are involved between T2DM and the development of PC [28].…”

Section: Genetic Mutations Driving Pancreatic Cancermentioning

confidence: 99%

The Role of Type 2 Diabetes in Pancreatic Cancer

George¹,

Jean-Baptiste²,

Ali³

et al. 2022

Cureus

View full text Add to dashboard Cite

The incidence of type 2 diabetes mellitus (T2DM) and its potential complications, such as cancers, are increasing worldwide at an astounding rate. There are many factors such as obesity, diabetes, alcohol consumption, and the adoption of sedentary lifestyles that are driving pancreatic cancer (PC) to become one of the leading causes of cancer mortality in the United States. PC is notorious for its generic symptoms and late-stage presentation with rapid metastasis. The connection between T2DM and the risk of PC development is multifaceted and complex. Some of the proposed theories reveal that chronic inflammation, insulin resistance, hyperinsulinemia, hyperglycemia, and abnormalities in the insulin and insulin-like growth factor axis (IGF) contribute to the disease association between these two conditions. This literature review aims to highlight relevant studies and explore the molecular mechanisms involved in the etiology of diabetes and its impact on PC development, as well as the role of anti-diabetic agents on PC. Despite extensive studies, the exact interaction between T2DM and PC remains obscure and will need further investigation. According to current knowledge, there is a substantial link between diabetes, obesity, and dietary patterns in the development and progression of PC. Consequently, focusing our efforts on preventive measures by reducing modifiable risk factors remains the most effective strategy to reduce the risk of PC at this time. Antidiabetic drugs can have various effects on the occurrence and prognosis of PC with metformin offering a clear benefit of inhibiting PC and insulin increasing the risk of PC. The development of future novel therapies will require a deeper knowledge of the triggering mechanisms and interplay between these two disease states.

show abstract

“…Heterozygous mutations in some of these genes, such as PDX1 and HNF1A, also lead to different types of monogenic diabetes in young people (types 4 and 5). Some variants in PDX1 and HNF1A are also associated with an increased risk of T2DM (64,65), obesity, or hyperglycemia (66).…”

Section: Genetics Factors Driving Dm and Pcmentioning

confidence: 99%

Type 2 Diabetes Mellitus Intersects With Pancreatic Cancer Diagnosis and Development

et al. 2021

View full text Add to dashboard Cite

The relationship between type 2 diabetes mellitus (T2DM) and pancreatic cancer (PC) is complex. Diabetes is a known risk factor for PC, and new-onset diabetes (NOD) could be an early manifestation of PC that may be facilitate the early diagnosis of PC. Metformin offers a clear benefit of inhibiting PC, whereas insulin therapy may increase the risk of PC development. No evidence has shown that novel hypoglycemic drugs help or prevent PC. In this review, the effects of T2DM on PC development are summarized, and novel strategies for the prevention and treatment of T2DM and PC are discussed.

show abstract

Molecular Dynamics Simulations Predict that rSNP Located in the HNF-1α Gene Promotor Region Linked with MODY3 and Hepatocellular Carcinoma Promotes Stronger Binding of the HNF-4α Transcription Factor

Cited by 5 publications

References 49 publications

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

The Role of Type 2 Diabetes in Pancreatic Cancer

Type 2 Diabetes Mellitus Intersects With Pancreatic Cancer Diagnosis and Development

Contact Info

Product

Resources

About